Allergy, eosinophilic inflammation, and epithelial dysregulation are implicated in severe asthma pathogenesis.We characterized biomarker expression in adults with severe asthma.Within the International Severe Asthma Registry (ISAR), we analyzed data from 10 countries in North America, Europe, and Asia, with prespecified thresholds for biomarker positivity (serum IgE ≥ 75 kU/L, blood eosinophils ≥ 300 cells/μL, and FeNO ≥ 25 ppb), and with hierarchical cluster analysis using biomarkers as continuous variables.Of 1,175 patients; 64% were female, age (mean ± SD) 53 ± 15 years, body mass index (BMI) 30 ± 8, postbronchodilator forced expiratory volume in 1 second (FEV1) predicted 72% ± 20%. By prespecified thresholds, 59% were IgE positive, 57% eosinophil positive, and 58% FeNO positive. There was substantial inflammatory biomarker overlap; 59% were positive for either 2 or 3 biomarkers. Five distinct clusters were identified: cluster 1 (61%, low-to-medium biomarkers) comprised highly symptomatic, older females with elevated BMI and frequent exacerbations; cluster 2 (18%, elevated eosinophils and FeNO) older females with lower BMI and frequent exacerbations; cluster 3 (14%, extremely high FeNO) older, highly symptomatic, lower BMI, and preserved lung function; cluster 4 (6%, extremely high IgE) younger, long duration of asthma, elevated BMI, and poor lung function; cluster 5 (1.2%, extremely high eosinophils) younger males with low BMI, poor lung function, and high burden of sinonasal disease and polyposis.There is significant overlap of biomarker positivity in severe asthma. Distinct clusters according to biomarker expression exhibit unique clinical characteristics, suggesting the occurrence of discrete patterns of underlying inflammatory pathway activation and providing pathogenic insights relevant to the era of monoclonal biologics.
Background: The International Severe Asthma Registry (ISAR) defines severe asthma as those on GINA step 5 or uncontrolled on step 4. These patients should be referred to specialist providers. But, severity may be mis-estimated in primary care and/or unrecognized (ie never referred to specialist care). Aim: To identify potential severe asthma patients in UK primary care. Methods: A historical cohort study was conducted using the Optimum Patient Care Research Database. Eligible patients had an active diagnosis of asthma (pre 2014), were ≥16 yrs old, and had ≥1 asthma medication within the past year. Patients were categorized according to GINA step and number exacerbations/yr. % of patients on GINA step 4 or 5 with no recorded specialist referral was also assessed. Results: 207,695 patients were included. 2.3% of GINA step 1 patients had ≥2 exacerbations/yr, rising to 3.2%, 5.0%, 12.8%, and 40.9% of those on GINA steps 2, 3, 4 and 5, respectively (Figure). 89.8% of patients at GINA step 5 or uncontrolled on step 4 had no specialist contact recorded in their last year of available data. Conclusion: The prevalence of severe asthma may be higher than previously estimated. Treatment resistant asthma due to other factors (e.g. adherence, technique, co-morbidities) cannot be discounted. Further analyses using detailed referral information will be undertaken and outcomes for unrecognized severe asthma patients in UK primary care compared with ISAR data.
Abstract The uncertainty around coronavirus disease-19 (COVID-19) has triggered anxiety among public. We aimed to assess the variation in anxiety and risk perceptions of COVID-19 among adults in Singapore. We administered a web-survey to a panel of residents between 31 March and 14 April 2020. We assessed anxiety using general anxiety disorder (GAD) scale and assessed participants’ risk perceptions regarding severity of the outbreak. Of the 1,017 participants, 23% reported moderate to severe anxiety [GAD score≥10]. A high proportion reported perceived likelihood of ICU admission (46%) and death (30%) upon getting COVID-19. Results from path analysis showed that younger participants, those with chronic conditions, those living with children and low perceived trust in government response to COVID-19 had a significantly higher anxiety mediated by their perceived risk of dying upon getting COVID-19. These results highlight the need for management of anxiety through adequate and effective risk communication for the general public.
Abstract Objectives To assess the extent to which public support for outbreak containment policies varies with respect to the severity of an infectious disease outbreak. Methods A web-enabled survey was administered to 1,017 residents of Singapore during the COVID-19 pandemic, and was quota-sampled based on age, gender and ethnicity. A fractional-factorial design was used to create hypothetical outbreak vignettes characterised by morbidity and fatality rates, and local and global spread of an infectious disease. Each respondent was asked to indicate which response policies (among 5 policies restricting local movement and 4 border control policies) they would support in 5 randomly-assigned vignettes. Binomial logistic regressions were used to predict the probabilities of support as a function of outbreak attributes, personal characteristics and perceived policy effectiveness. Results Likelihood of support varied across government response policies; however, was generally higher for border control policies compared to internal policies. The fatality rate was the most important factor for internal policies while the degree of global spread was the most important for border control policies. In general, individuals who were less healthy, had higher income and were older were more likely to support these policies. Perceived effectiveness of a policy was a consistent and positive predictor of public support. Conclusions Our findings suggest that campaigns to promote public support should be designed specifically to each policy and tailored to different segments of the population. They should also be adapted based on the evolving conditions of the outbreak in order to receive continued public support.
Abstract Objectives Older adults with severe dementia experience multiple symptoms at the end of life. This study aimed to delineate distinct symptom profiles of older adults with severe dementia and to assess their association with older adults’ and caregiver characteristics and 1-year mortality among older adults. Methods We used baseline data from a cohort of 215 primary informal caregivers of older adults with severe dementia in Singapore. We identified 10 indicators representing physical, emotional, and functional symptoms, and responsive behaviors, and conducted latent class analysis. We assessed the association between delineated older adults’ symptom profiles and their use of potentially burdensome health-care interventions in the past 4 months; older adults’ 1-year mortality; and caregiver outcomes. Results We delineated 3 profiles of older adults – primarily responsive behaviors (Class 1; 33%); physical and emotional symptoms with responsive behaviors (Class 2; 20%); and high functional deficits with loss of speech and eye contact (Class 3; 47%). Classes 2 and 3 older adults were more likely to have received a potentially burdensome intervention for symptoms in the past 4 months and have a greater hazard for 1-year mortality. Compared to Class 1, caregivers of Class 2 older adults were more likely to experience adverse caregiver outcomes, that is, higher distress, impact on schedule and health, anticipatory grief, and coping and lower satisfaction with care received ( p <0.01 for all). Significance of results The 3 delineated profiles of older adults can be used to plan or optimize care plans to effectively manage symptoms of older adults and improve their caregivers’ outcomes.
ABSTRACT Incidence of adverse outcome events rises as patients with advanced illness approach end‐of‐life. Exposures that tend to occur near end‐of‐life, for example, use of wheelchair, oxygen therapy and palliative care, may therefore be found associated with the incidence of the adverse outcomes. We propose a concept of reverse time‐to‐death (rTTD) and its use for the time‐scale in time‐to‐event analysis based on partial likelihood to mitigate the time‐varying confounding. We used data on community‐based palliative care uptake (exposure) and emergency department visits (outcome) among patients with advanced cancer in Singapore to illustrate. We compare the results against that of the common practice of using time‐on‐study (TOS) as time‐scale. Graphical analysis demonstrated that cancer patients receiving palliative care had higher rate of emergency department visits than non‐recipients mainly because they were closer to end‐of‐life, and that rTTD analysis made comparison between patients at the same time‐to‐death. In analysis of a decedent cohort, emergency department visits in relation to palliative care using TOS time‐scale showed significant increase in hazard ratio estimate when observed time‐varying covariates were omitted from statistical adjustment (% change‐in‐estimate = 16.2%; 95% CI 6.4% to 25.6%). There was no such change in otherwise the same analysis using rTTD (% change‐in‐estimate = 3.1%; 95% CI ‐1.0% to 8.5%), demonstrating the ability of rTTD time‐scale to mitigate confounding that intensifies in relation to time‐to‐death. A similar pattern was found in the full cohort. Simulations demonstrated that the proposed method had smaller relative bias and root mean square error than TOS‐based analysis. In conclusion, use of rTTD as time‐scale in time‐to‐event analysis provides a simple and robust approach to control time‐varying confounding in studies of advanced illness, even if the confounders are unmeasured.
Objective We investigated the variation in patient-reported decision-making roles in the past year of life among patients with metastatic solid cancer and the associations of these roles with patient quality of life and perceived quality of care. Methods We used the last year of life data of 393 deceased patients from a prospective cohort study. Patients reported their decision-making roles, quality of life (emotional well-being, spiritual well-being, and psychological distress) and perceived quality of care (care coordination and physician communication) every 3 months until death. We used mixed effects linear regressions to investigate the associations of decision-making roles with patients’ quality of life and perceived quality of care. Results The most reported roles, on average, were patient-led (37.9%) and joint (23.4%; with physicians and/or family caregivers) decision making, followed by no patient involvement (14.8%), physician/family-led (12.9%), and patient alone (11.0%) decision making. Patient level of involvement in decision making decreased slightly as death approached ( P < 0.05). Compared with no patient involvement, joint decision making was associated with better emotional well-being (β [95% confidence interval] = 1.02 [0.24, 1.81]), better spiritual well-being (1.48 [0.01, 2.95]), lower psychological distress (−1.99 (−3.21, −0.77]), higher perceived quality of care coordination (5.04 [1.24, 8.85]), and physician communication (5.43 [1.27, 9.59]). Patient-led decision making was associated with better spiritual well-being (1.69 [0.24, 3.14]) and higher perceived quality of care coordination (6.87 [3.17, 10.58]) and physician communication (6.21 [2.15, 10.27]). Conclusion Joint and patient-led decision-making styles were reported by 61% of the patients and were associated with better quality of life and quality of care. A decrease in the level of patient involvement over time indicates reliance on family and physicians as death approached. Highlights Among patients with metastatic cancer, the level of patient involvement in decision making decreased slightly as death approached. Joint decision making of patients with their physicians and/or family caregivers and patient-led decision making were associated with better quality of life and perceived quality of care. Patients with metastatic cancer should be encouraged to be involved in decision making together with their physicians and/or family caregivers to potentially improve their end-of-life experience.
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